Porth's Essentials of Pathophysiology, 4e

531

Control of Respiratory Function

C h a p t e r 2 1

The term affinity refers to hemoglobin’s ability to bind oxygen. Hemoglobin binds oxygen more readily when its affinity is increased and releases it more readily when its affinity is decreased. The hemoglobin molecule is composed of four poly- peptide chains with an iron-containing heme group (see Chapter 14, Fig. 14-2). Because oxygen binds to the iron atom, each hemoglobin molecule can bind four mole- cules of oxygen when it is fully saturated. Oxygen binds cooperatively with the heme groups on the hemoglo- bin molecule. After the first molecule of oxygen binds to a heme group, the hemoglobin molecule undergoes a change in shape. As a result, the second and third molecules of oxygen bind more readily, and binding of the fourth molecule is even easier. In a like manner, the unloading of the first molecule of oxygen enhances the unloading of the next molecule and so on. Thus, the affinity of hemoglobin for oxygen changes with hemo- globin saturation. Hemoglobin’s affinity for oxygen is also influenced by pH, carbon dioxide concentration, and body tem- perature. It binds oxygen more readily under conditions of increased pH (alkalosis), decreased carbon dioxide concentration, and decreased body temperature and it releases it more readily under conditions of decreased pH (acidosis), increased carbon dioxide concentration, and fever. For example, increased tissue metabolism gen- erates carbon dioxide and metabolic acids and thereby decreases the affinity of hemoglobin for oxygen. Heat also is a by-product of tissue metabolism, explaining the effect of fever on oxygen binding. Red blood cells contain a metabolic intermedi- ate called 2,3-diphosphoglycerate (2,3-DPG) that also affects the affinity of hemoglobin for oxygen. An increase in 2,3-DPG enhances unloading of oxygen from hemoglobin at the tissue level. Conditions that increase 2,3-DPG include exercise, hypoxia that occurs at high altitude, and chronic lung disease. ) of oxygen represents the level of dissolved oxygen in plasma. The amount of dissolved oxygen that is carried in the plasma depends on its par- tial pressure and its solubility in the plasma. The PO 2 of the arterial blood normally ranges from 85 to 100 mm Hg when breathing room air at 1 atmosphere (760 mm Hg). The solubility of oxygen in plasma is fixed and very small. For every 1 mm Hg of PO 2 present, 0.03 mL of oxygen becomes dissolved in 1 dL of plasma. This means that at a normal arterial PO 2 of 95 mm Hg, about 0.29 mL of oxygen is dissolved in every dL of plasma. Therefore, the amount of oxygen transported in the dissolved state is very small, only about 3% of the total, as compared with the 97% transported by the hemoglobin. Although the amount of oxygen carried in plasma under normal conditions is small, it can become a life- saving mode of transport in cases of carbon monoxide poisoning, when most of the hemoglobin sites are occu- pied by carbon monoxide and are unavailable for trans- port of oxygen. Carbon monoxide, which combines PlasmaTransport The partial pressure (PO 2

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Normal Hb

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FIGURE 21-17. Oxygen-hemoglobin dissociation curve. (A) Left boxed area represents the steep portion of the curve where oxygen is released from hemoglobin (Hb) to the tissues, and the top boxed area on the plateau of the curve where oxygen is loaded onto hemoglobin in the lung. P 50 is the partial pressure of oxygen required to saturate 50% of hemoglobin with oxygen. (B) The effect of body temperature, arterial PCO 2 , and pH on hemoglobin affinity for oxygen as indicated by a shift in the curve and position of the P 50 . A shift of the curve to the right due to an increase in temperature or PCO 2 or a decrease in pH favors release of oxygen to the tissues. A decrease in temperature or PCO 2 or an increase in pH shifts the curve to the left. (C) Effect of anemia on the oxygen-carrying capacity of blood. The hemoglobin can be completely saturated, but the oxygen content of the blood is reduced. (Adapted from Rhoades RA, Tanner GA. Medical Physiology. Boston, MA: Little, Brown; 1996.) ( text continues on page 533 )